Deoxyspergualin therapy in autoimmune MRL/1pr mice suffering advanced lupus-like disease.
The present study was designed to evaluate the therapeutic activity of a novel immunosuppressive agent, deoxyspergualin (DSG, NKT-01) in male MRL/MpJ-lpr/lpr (MRL/lpr) mice suffering advanced systemic lupus erythematosus (SLE)-like lesions. Treatment with DSG in the early phase of the disease at doses of 1.5 and 3 mg/kg strongly suppressed the development of SLE-like lesions. When DSG was administered from week 21 through 29 to MRL/lpr mice in advanced phases of the disease, a daily iv dose of 3 mg/kg (5 days/week) markedly reduced the symptoms, whereas a dose of 1.5 mg/kg did not. Moreover, DSG treatment at a dose of 3mg/kg, started at the time when the blood urea nitrogen levels were over 50 mg/deciliter, significantly prevented deterioration of the hyperuremia. Taking these findings into consideration, DSG was found to be a promising agent for curing such established autoimmune disease.
Nemoto
K
K
Research Laboratories, Pharmaceuticals Group, Nippon Kayaku Co., Ltd., Tokyo, Japan.
Mae
T
T
Sugawara
Y
Y
Hayashi
M
M
Abe
F
F
Takeuchi
T
T
D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications / Q000188:drug therapy*; D001806:Blood Urea Nitrogen; D004305:Dose-Response Relationship, Drug; D005921:Glomerulonephritis / Q000209:etiology / Q000517:prevention & control; D006146:Guanidines / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051379:Mice; D014511:Uremia / Q000188:drug therapy
D006146:Guanidines; D007166:Immunosuppressive Agents; C037258:gusperimus